A combination of genes and environment

Multiple sclerosis occurs in people with genetic susceptibility factors to the disease, which interact with various external factors from the environment. The low concordance rate between identical twins underlines the importance of such environmental factors. Beyond a certain, as yet undefined, threshold, tolerance to the autoantigens of the central nervous system is broken and the central nervous system is affected by focal inflammatory lesions caused by the hyperactivation of a disturbed immune system.

A great deal of research concerns the environmental factors which may trigger the disease in a susceptible individual. Two of them have been firmly established which can be controlled or corrected: smoking and Vitamin D deficiency.

Giving up smoking protects the nervous system

Many studies have shown that beginning to smoke during adolescence increases the risk of developing multiple sclerosis and that this risk depends on both the number of years and the quantity of cigarettes smoked. The fact of smoking 5 cigarettes a day for 15 years multiplies the risk by 1.5, while heavy smoking (20-40 cigarettes a day) multiplies it by 2. Passive smoking is also involved, for instance in teenagers under 16 who develop the disease. A Swedish study has recently shown that the excess number of cases of multiple sclerosis caused by active or passive smoking  accounts for 22% of multiple sclerosis patients. 

If the patient continues to smoke after the first episode has been diagnosed, he or she is more susceptible  having a relapse sooner, displaying larger numbers of lesions detectable by brain resonance imaging, developing cerebral atrophy, and entering the secondary progressive phase of the disease. On average, the entry into the progressive phase occurs 8 years earlier in smokers than in non-smokers. On the contrary, when the patient ceases to smoke at the time of diagnosis (i.e. gives it up completely, as even a single cigarette a day has a negative impact), the consequences of smoking disappear in around 10 years and the disease evolves in the same way as in non-smokers.

What is toxic is tobacco smoke rather than tobacco itself. As a result, the first measure to protect the nervous system is to give up smoking completely. It should be ensured that the children of MS patients are not exposed to passive  smoke and do not begin to smoke in adolescence, as they already have a higher risk of developing multiple sclerosis (a risk of 2.5%, against 0.1% among the general population).

Taking Vitamin D: a precaution

Vitamin D deficiency is frequent in Northern Europe as 90% of Vitamin D is synthesized in the skin under the effect of the sun’s ultraviolet irradiation. Low Vitamin D blood levels in childhood and adolescence are a factor in the development of multiple sclerosis in adulthood. In a Finnish study published in March 2016, mothers with inadequate Vitamin D levels in early pregnancy almost doubled the risk of their children developing multiple sclerosis. Not only this vitamin is important to calcium and bone metabolism, but also aids the maturation of the immune system and has immunomodulating properties. The prevalence of the disease is twice as high in the North and East of France as in Provence and the Côte d’Azur; this prevalence is in reverse proportion to the ultraviolet irradiation in these areas and to the average Vitamin D blood levels of the populations concerned. In MS patients, low Vitamin D levels are associated with increased disease activity detected by brain resonance imaging.

This inverted ratio was particularly observed in two studies of interferon beta 1b (Betaferon), the BENEFIT and BEYOND studies. The presence of a high Vitamin D blood level, between 40 and 60 ng/ml, decreased the number of active lesions detected by brain imaging by almost 50%. These studies also demonstrated a synergetic effect between Vitamin D and beta interferon, which has not yet been demonstrated in the case of glatiramer acetate or other immunomodulating treatments used in the disease.

Vitamin D is not toxic, even when taken at high doses, up to 20,000 units per day (one ampoule of D Cure contains 25,000 units). In the current state of knowledge, maintaining a Vitamin D blood level of 40 to 60 ng/ml in MS patients – and in their children – is a justified precaution. Two placebo-controlled scientific studies concerning the addition of Vitamin D to the treatment of multiple sclerosis patients are under way or nearing completion (EVIDIMS and SOLAR). Their results will be important in the generalisation of Vitamin D as an additional therapy for multiple sclerosis.

Prof. Christian Sindic